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Thomas, L.

Publications and source records attributed to Thomas, L..

At least 19 recordsLinked to original sources

The tiger shark, Galeocerdo cuvier (Peron & Lesueur, 1822), genome reveals genomic and epigenomic signatures of shark evolution and demographic history

Cartilaginous fishes (Chondrichthyes) represent one of the oldest extant vertebrate lineages, persisting for over 450 million years, yet genomic resources remain limited for many species despite widespread conservation concern. The tiger shark, Galeocerdo cuvier (Peron & Lesueur, 1822), the sole surviving member of the family Galeocerdonidae, is a circumglobally cosmopolitan predator vital in ecosystem regulation but is experiencing population declines. Here, we generated the first chromosome-scale haplotype-phased reference genome for the tiger shark and integrated comparative and population genomics with methylomics to characterise its genome architecture and evolutionary history. This assembly presented the first evidence of male heterogamety in this species. Comparative analyses revealed lineage-specific transposable element expansions across the chondrichthyan class suggesting ongoing genome restructuring in Carcharhiniform sharks. We report the first hydroxymethylome in a chondrichthyan, higher than that of other vertebrates, hinting at novel DNA evolutionary and regulatory pathways in an early-diverging lineage of jawed vertebrates. We identified genomic signatures of prolonged population decline that correlated with historical climate fluctuations and have resulted in sustained low levels of genetic heterozygosity in this species. These findings offer new insights into shark and broader vertebrate genomic and epigenomic evolution while providing valuable resources for conservation genomics of one of the world's most widespread top-order predators in the face of accelerating environmental change.

genomics↗

When blood is not thicker than water: Social information landscapes offset the food-fear trade-off in habitat selection decisions

1. Group foraging reduces the risks associated with foraging: larger groups dilute individual predation risk, allow group members to share the costs of vigilance, and provide a social structure for exchanging information about predators. The benefits of shared social information over simple safety in numbers should depend on the relationships among group members. Consequently, group composition should affect the selection of risky and safe habitats in social species. 2. We asked whether relationships among elk (Cervus canadensis) group members moving together influence their selection of risky habitats more than grouping alone. We tested three hypotheses. The familiarity hypothesis predicts that elk with close social ties are most likely to select risky habitats together. The inclusive fitness hypothesis predicts that the closest genetic relatives are most likely to select risky habitats together. The dilution hypothesis predicts that familiarity and genetic relationships do not influence habitat selection, with all group foraging benefits derived from proximity to others. 3. We used integrated Step Selection Analysis to test whether the identity of the closest group members influenced habitat selection. We tested whether the relationship of the nearest elk--either genetic or social--incentivized selection of risky habitat more than proximity to the nearest elk. 4. Group foraging clearly reduced risk, with elk more likely to select risky habitat when near others. Elk were also more likely to select risky habitats when near closer relatives, albeit with considerable variation among individuals. However, familiarity had a large and consistent effect: elk were far more likely to select risky habitats when near socially familiar group members. 5. Our results suggest that information shared within foraging groups, especially between socially familiar individuals, may lower the risks associated with habitat selection. Similarly, the benefits of reliable social information for reducing risk likely incentivizes the formation of stronger social ties within foraging groups. This positive feedback between social familiarity and habitat selection could thereby increase access to profitable habitats that are otherwise too risky, cementing what we term the social information landscape as a key driver of movement and habitat selection.

ecology↗

Spatiotemporal data integration for marine megafauna SDMs in dynamic environments: A point process approach

Species distribution models (SDMs) are widely used to predict where and when species occur, but the data available to fit them often resolve space and time unevenly. Designed surveys, such as line-transect distance-sampling surveys, provide structured spatial coverage and the detection information needed to estimate detectability, but logistical and funding constraints often limit them to short, infrequent periods. Opportunistic or citizen-science records are collected more frequently across the year, but from areas shaped by observer access and interest rather than survey design, and usually without comparable detection information. As a result, models built from either source alone tend to capture spatial structure or temporal dynamics well, but not both, limiting predictions for mobile species in dynamic environments. Here, we present a general framework, based on a log-Gaussian Cox process (LGCP) fitted using integrated nested Laplace approximations (INLA), that links multiple data sources to a shared spatiotemporal measure of species density through source-specific observation models: a detection function for survey transects, and spatial constraints reflecting the footprint of opportunistic effort. We apply the framework to cetacean line-transect surveys and whale-watching records. In a simulation with one month of survey data and twelve months of opportunistic data, the integrated model recovered spatiotemporal distribution patterns well (median correlation with the true pattern = 0.91) and estimated monthly abundance with a mean error of +10.7%, outperforming single-source models. In a case study of common dolphins (Delphinus delphis) off mainland Portugal, integration improved the spatial accuracy of predictions, although weak covariate effects limited the temporal variation the model could resolve. These results show that integration adds the most value when the two data sources resolve complementary aspects of distribution, in this case broad spatial structure from the survey and temporal replication from whale-watching, while temporal predictions remain limited when covariates carry weak seasonal signal. The framework is general and can be extended to other taxa, systems, and combinations of structured and opportunistic data by substituting the relevant observation models.

ecology↗

Sustainable cattle management by communities supports African wildlife

Community-based conservation (CBC) initiatives aim to reconcile biodiversity protection with local livelihoods, yet their effectiveness in protecting wildlife remains uncertain, often hinging on local management1,2. We evaluated a globally significant CBC model in Kenyas Greater Maasai Mara Ecosystem (GME), where conservancies, run jointly by Maasai landowners and the tourism sector, employ rotational cattle grazing to support both wildlife and pastoralism3,4. Using a [~]1200 km2 grid of 180 camera traps across gradients of livestock pressure in Maasai Mara National Reserve and three conservancies in 2018, we collected and analysed over 2 million images with a customised AI-powered pipeline. We found a positive impact of observed cattle pressure on mammal community occupancy and species richness, except for at the highest levels of cattle grazing. However, sheep and goat grazing and proximity to infrastructure had a negative impact. These results provide evidence that wildlife and pastoralism can coexist under community-led stewardship5, but only with active management and targeted control of emerging threats. AI tools such as our image classifier may contribute to more adaptive community-led management of these areas6. As conservation policy shifts beyond formal protected areas, our findings support CBC as a scalable model for conserving biodiversity within working landscapes, offering a pathway to meet global targets while maintaining local livelihoods7.

ecology↗

Microbial and small zooplankton communities predict density of baleen whales in the southern California Current Ecosystem

Understanding the density of marine mammals is important for assessing population dynamics and evaluating the impacts of human activities on these species. In this work, we examine microorganisms that may be ecologically associated, whether directly or indirectly, with baleen whales - the potential "ecological habitat" - to predict baleen whale densities via statistical relationships adjusted for seasonal patterns of occurrence. We assessed the capability of microbial and small plankton communities to predict the density of Balaenopteridae whales in the Southern California Current Ecosystem in each quarterly season from 2014 to 2020 using data from the California Cooperative Oceanic Fisheries Investigations (CalCOFI). Densities were estimated from visual sightings for three target species - blue, fin, and humpback whales - and microbial and small plankton communities were examined using concurrent water samples via metabarcoding of the 16S and 18S rRNA genes. We identified microbial and small plankton communities specific to each target species that were strong predictors of estimated density. Groups of 23-60 distinct Amplicon Sequence Variants (ASVs) per baleen whale species explained 81-99% of variability in estimated whale density and predicted density estimates to within [~]1 individual per 1000 km2. The predictive accuracy achieved by our approach, compared with naive seasonal carry-forward and seasonal averaging approaches to prediction, improves out-of-sample RMSE by up to an estimated 65%. Microbial and small plankton communities were characterized by 148 unique taxonomic annotations enumerated across marker genes. Of these, 20% were shared across all three species, 21% were shared by two species, and the remaining (59%) were unique to a single whale species, which suggests that there is some overlap in the ecological habitat among blue, humpback, and fin whales, but each species is also related to a distinct community of microbes and small plankton. We also conducted a narrative review to examine existing known relationships of baleen whales with microbes or small plankton. Of the 148 unique taxonomic annotations we found to be predictive of baleen whale densities, 23% have been referenced within the existing literature exploring microbial prey, parasites, commensals, or respiratory-associated organisms of baleen whales, with matches at the genus or family level. The rest matched at higher taxonomic levels (41%) or had no documented matches in our literature search (36%). These findings suggest that some of the microbial and small plankton community predictors may be ecologically relevant, yet further studies are needed to understand how these organisms function collectively as a community and interact with whale ecology, prey, and the surrounding environment. Our results suggest that using microbial and small plankton communities to quantify the potential ecological habitat of larger organisms, like baleen whales, can enhance predictive models and may inform hypotheses about the ecological relationships between whales and the biological communities with which they co-occur.

ecology↗

Multigenerational Tracking of Reef-Building Corals Using CRISPR-Cas9induced Genetic Barcodes and eDNA Metabarcoding

Widespread biodiversity loss driven by human activity has intensified global efforts to restore degraded ecosystems. Yet a key challenge remains: how to track restored individuals and their offspring over time and space to assess the true impact of restoration? This is especially pressing for coral reefs, which support a quarter of all marine species, are in severe decline globally, and are now the focus of growing restoration initiatives worldwide. Here, we demonstrate a novel approach that combines genome editing and environmental DNA (eDNA) monitoring to enable scalable, non-invasive tracking of individual corals and their offspring. Using CRISPR-Cas9, we introduced unique genetic barcodes into non-coding regions of the Acropora millepora genome. These barcodes - stable, heritable, and distributed across the genome - will allow for individual-level identification over multiple generations. We show that these barcodes can be reliably detected in surrounding seawater using eDNA metabarcoding, offering a powerful, non-destructive tool for tracking corals in situ. Together, this approach provides a proof-of-concept for precision monitoring of restoration outcomes, with broad applicability across species and ecosystems.

genetics↗

Population genetic assessment of marine megafauna using seawater environmental DNA: a case study of whale sharks from the Ningaloo Coast World Heritage Area.

There is a growing need for scalable and cost-effective genetic monitoring tools to support the management of species and populations of conservation importance, driven by the increasing biodiversity loss, need for long-term population data and limitations of invasive genetic sampling. Whale sharks (Rhincodon typus), along with other Endangered, elusive and highly migratory species, spend the majority of their lives in offshore ocean waters. This behaviour poses logistical and ethical challenges to invasive genetic sampling of the species, which is traditionally done via tissue biopsy. Here, we develop a genetic toolkit to study populations of whale sharks from seawater environmental DNA using short segments of nuclear DNA (100-300bp) containing two or more SNPs called "microhaplotypes". Amplifying these markers from seawater collected in 1L bottles behind sharks showed that we can reliably genotype sharks from water samples taken immediately behind the animal. Moreover, we observed a strong relationship between population-level allele frequencies and estimates of genetic diversity between eDNA and tissue-derived samples, demonstrating the capability of eDNA in capturing population-level genetic information with high fidelity. We also analysed a tissue dataset of 72 sharks that attended the Ningaloo Coast World Heritage Area over six-years to showcase the utility of our SNP panel to study temporal processes in these populations. Our data revealed patterns of genetic variation through time that were consistent with whole genome techniques. Contributor estimation from mock environmental samples using various combinations of tissue-derived sequence data to estimate abundance of animals in a mixed DNA sample was shown to accurately identify the number of contributors in mixtures containing [≤] 10 individuals, beyond which biases were too large. Our findings illustrate the viability of using microhaplotype markers from seawater eDNA as a tool to study conservation genetics of whale sharks, with the potential for broader expansion of eDNA-based genetic assessments to other marine megafauna and aquatic species.

genetics↗

Metalog: curated and harmonised contextual data for global metagenomics samples

Metagenomic sequencing enables the in-depth study of microbes and their functions in humans, animals and the environment. While sequencing data is deposited in public databases, the associated contextual data is often not complete and needs to be retrieved from primary publications. This lack of access to sample-level metadata like clinical data or in situ observations impedes cross-study comparisons and meta-analyses. We therefore created the Metalog database, a repository of manually curated metadata for metagenomics samples across the globe. It contains 73,082 samples from humans (including 58,506 of the gut microbiome), 10,703 animal samples, 5,146 ocean water samples, and 21,802 samples from other environmental habitats such as soil, sediment, or fresh water. Samples have been consistently annotated for a set of habitat-specific core features, such as demographics, disease status and medication for humans, host species and captivity status for animals, and filter sizes and salinity for marine samples. Additionally, all original metadata is provided in tabular form, simplifying focused studies e.g. into nutrient concentrations. Pre-computed taxonomic profiles facilitate rapid data exploration, while links to the SPIRE database enable genome-based analyses. The database is freely available for browsing and download at https://metalog.embl.de/.

microbiology↗

The Green Band: Using Production and Catch to Judge Distortive Pressure on an Ecosystem

Ecosystem based fisheries management is an increasingly accepted approach for many fisheries management agencies. Indicators and methods that can usefully support the aspiration of making ecosystem based fisheries management decisions on tactical time frames are slowly accumulating, but have primarily focused on biomass status and trends. We first verify that fishing can distort the cumulative distribution of connections within an ecosystem, and then show (via theoretical testing and application to four contrasting case study locations) how relating catch with production by defining an acceptable band of exploitation pressure - the "Green Band" - can help inform fisheries decision makers as to whether an ecosystem is under distortive patterns of fishing pressure that will ultimately undermine the structure of the ecosystem.

ecology↗

Transmembrane Serine Protease TMPRSS11B promotes an acidified tumor microenvironment and immune suppression in lung squamous cell carcinoma

Lung cancer is the leading cause of cancer-related deaths worldwide. Existing therapeutic options have limited efficacy, particularly for lung squamous cell carcinoma (LUSC), underscoring the critical need for the identification of new therapeutic targets. We previously demonstrated that the Transmembrane Serine Protease TMPRSS11B promotes transformation of human bronchial epithelial cells and enhances lactate export from LUSC cells. To determine the impact of TMPRSS11B activity on the host immune system and the tumor microenvironment (TME), we evaluated the effect of Tmprss11b depletion in a syngeneic mouse model. Tmprss11b depletion significantly reduced tumor burden in immunocompetent mice and triggered an infiltration of immune cells. RNA FISH analysis and spatial transcriptomics in the autochthonous Rosa26-Sox2-Ires-GfpLSL/LSL; Nkx2-1fl/fl; Lkb1fl/fl (SNL) model revealed an enrichment of Tmprss11b expression in LUSC tumors, specifically in Krt13+ hillock-like cells. Ultra-pH sensitive nanoparticle imaging and metabolite analysis identified regions of acidification, elevated lactate, and enrichment of M2-like macrophages in LUSC tumors. These results demonstrate that TMPRSS11B promotes an acidified and immunosuppressive TME and nominate this enzyme as a therapeutic target in LUSC.

cancer biology↗

TL1A overexpression in Crohn's Disease and mice alters Paneth cells and microbiota promoting ileal inflammation

Paneth cells regulate host-microbial homeostasis and defects in autophagy and host defense pathways have been associated with inflammatory bowel diseases (IBD). Genetic variants in TL1A (TNFSF15) and its receptor DR3 (TNFRSF25) have been associated with IBD. TL1A expression is increased in IBD patients, particularly in TL1A risk allele carriers. However, effects of TL1A on Paneth cells, resident microbiota, and development of ileitis remain unknown. TL1A overexpression in mice induces Paneth cell hyperplasia and morphological abnormalities preceding the development of ileitis. In Crohns disease (CD) patients, ileal TL1A expression was associated with abnormal Paneth cell phenotypes. We confirmed direct effects of TL1A on Paneth cells in human iPSC-derived human intestinal organoids and mouse Paneth cell-enriched organoids. Resident microbiota was required for TL1A-mediated Paneth cell dysfunction, and ileitis. Tl1a-tg mice were enriched in short chain fatty acid-producing bacteria and the metabolite acetate. Acetate supplementation in WT or Tl1a-tg mice caused ileal inflammation, suggesting that acetate is sufficient to cause ileitis. DR3-deficiency in Paneth cells resulted in Paneth cell abnormalities and microbiome composition changes. Our findings provide a mechanistic link between overexpression of TL1A in CD patients, Paneth cell dysfunction, and enrichment of acetate-producing bacteria and acetate that promotes ileal inflammation. Brief SummaryOverexpression of TL1A drives Paneth cell dysfunction in Crohns Disease and mice leading to microbial and metabolomic changes that promote small bowel inflammation.

immunology↗

Towards population genetic assessments and species abundance from environmental DNA: A case study with zebrafish in controlled aquaria

Developing robust methods for amplifying and analysing highly-polymorphic nuclear genetic markers from environmental samples could assist in the reliable and scalable long-term monitoring of elusive, threatened or invasive species that are otherwise challenging to observe. In this study, we used zebrafish in controlled aquaria to apply forensic science approaches and demonstrate that microhaplotypes, which are short segments of nuclear DNA (100-300bp) containing two or more single nucleotide polymorphisms (SNPs), can be amplified from trace DNA in water samples to accurately estimate population genetic diversity and species abundance. We successfully amplified a panel of 17 microhaplotypes that comprised 69 SNPs which could reliably estimate population-level allele frequencies and genetic diversity estimates from water DNA. The panel of microhaplotypes amplified from water samples from replicate tanks strongly matched allele frequency estimates from corresponding tissue samples, and could also be used for estimating number of contributors from multi-individual samples. Our research demonstrates the effectiveness and potential of amplifying microhaplotype panels from eDNA as a non-invasive and scalable tool for population genetic studies of aquatic species.

ecology↗

Helical transition of the bridge helix of Cas12a is an allosteric regulator of R-loop formation and RuvC activation

CRISPR-Cas12a is widely used for genome editing and biomarker detection since it can create targeted double-stranded DNA breaks and promote non-specific DNA cleavage after identifying specific DNA. To mitigate the off-target DNA cleavage of Cas12a, we previously developed a Francisella novicida Cas12a variant (FnoCas12aKD2P) by introducing double proline substitutions (K969P/D970P) in a conserved helix called the bridge helix (BH). In this work, we used cryogenic electron microscopy (cryoEM) to understand the molecular mechanisms of BH-mediated activation of Cas12a. We captured five structures of FnoCas12aKD2P at different states of conformational activation. Comparison with wild-type (FnoCas12aWT) structures unravels a mechanism where BH acts as a trigger that allosterically activates REC lobe movements by tracking the number of base pairs in the growing RNA-DNA hybrid to undergo a loop-to-helical transition and bending to latch onto the hybrid. The transition of the BH is coupled to the previously reported loop-to-helix transition of the "lid", essential for opening RuvC endonuclease, through direct interactions of residues of the BH and the lid. We also observe structural details of cooperativity of BH and "helix-1" of RuvC for activation, a previously proposed interaction. Overall, our study enables development of high-fidelity Cas12a and Cas9 variants by BH-modifications.

biochemistry↗

Categorical and semantic perception of the meaning of call-types in zebra finches

Vocal communication in social animals involves the production and perception of various calls that ethologists categorize into call-types, based on their acoustical structure and the behavioral context of production. Whether animals perceive these categories and associate distinct meanings to them remains unknown. The zebra finch, a gregarious songbird, uses approximately 11 call-types to communicate hunger, danger, social conflict, and establish social contact and bonding. Using auditory discrimination tasks, we show that the birds discriminate and categorize all the call-types in their vocal repertoire. In addition, systematic errors were more frequent between call-types used in similar behavioral contexts than could be expected from their acoustic similarity. Thus, zebra finches organize their calls into categories and create a mental representation of the meaning of these sounds.

animal behavior and cognition↗

Coordinated translational control of multiple immune checkpoints by the integrated stress response pathway in lung cancer

The integrated stress response (ISR) is an adaptive pathway hijacked by cancer cells to survive cellular stresses in the tumor microenvironment. ISR activation potently induces Programmed Death Ligand 1 (PD-L1), leading to suppression of anti-tumor immunity. Here we sought to uncover additional immune checkpoint proteins regulated by the ISR to elucidate mechanisms of tumor immune escape. We show that CD155 and PD-L1 are coordinately induced by the ISR, enhancing translation of both immune checkpoint proteins through bypass of inhibitory upstream open reading frames (uORFs) in their 5' UTRs. Analysis of primary human lung tumors identifies a significant correlation between PD-L1 and CD155 expression. ISR activation accelerates tumorigenesis and inhibits T cell function, effects that can be overcome by combining PD-1 blockade with the ISR inhibitor ISRIB. These studies uncover a novel mechanism by which two immune checkpoint proteins are coordinately regulated and suggest a new therapeutic strategy for lung cancer patients. Statement of SignificanceThis study uncovers a novel mechanism for the coordinated translational regulation of the PD- L1/PD1 and CD155/TIGIT immune checkpoint pathways and highlights the ISR as a therapeutic vulnerability for lung cancer. Inhibition of the ISR pathway bolsters PD-1 blockade, potentially unveiling a new therapeutic strategy for lung cancer patients.

cancer biology↗

Mechanisms of Nuclear Pore Complex disassembly by the mitotic Polo-Like Kinase 1 (PLK-1) in C. elegans embryos

The nuclear envelope, which protects and organizes the interphase genome, is dismantled during mitosis. In the C. elegans zygote, nuclear envelope breakdown (NEBD) of the parental pronuclei is spatially and temporally regulated during mitosis to promote the unification of the parental genomes. During NEBD, Nuclear Pore Complex (NPC) disassembly is critical for rupturing the nuclear permeability barrier and removing the NPCs from the membranes near the centrosomes and between the juxtaposed pronuclei. By combining live imaging, biochemistry, and phosphoproteomics, we characterized NPC disassembly and unveiled the exact role of the mitotic kinase PLK-1 in this process. We show that PLK-1 disassembles the NPC by targeting multiple NPC sub-complexes, including the cytoplasmic filaments, the central channel, and the inner ring. Notably, PLK-1 is recruited to and phosphorylates intrinsically disordered regions of several multivalent linker nucleoporins, a mechanism that appears to be an evolutionarily conserved driver of NPC disassembly during mitosis. (149/150 words) One-Sentence SummaryPLK-1 targets intrinsically disordered regions of multiple multivalent nucleoporins to dismantle the nuclear pore complexes in the C. elegans zygote.

cell biology↗

Flexible hidden Markov models for behaviour-dependent habitat selection

There is strong incentive to model behaviour-dependent habitat selection, as this can help delineate critical habitats for important life processes and reduce bias in model parameters. For this purpose, a two-stage modelling approach is often taken: (i) classify behaviours with a hidden Markov model (HMM), and (ii) fit a step selection function (SSF) to each subset of data. However, this approach does not properly account for the uncertainty in behavioural classification, nor does it allow states to depend on habitat selection. An alternative approach is to estimate both state switching and habitat selection in a single, integrated model called an HMM-SSF. We build on this recent methodological work to make the HMM-SSF approach more efficient and general. We focus on writing the model as an HMM where the observation process is defined by an SSF, such that well-known inferential methods for HMMs can be used directly for parameter estimation and state classification. We extend the model to include covariates on the HMM transition probabilities, allowing for inferences into the temporal and individual-specific drivers of state switching. We demonstrate the method through an illustrative example of African zebra (Equus quagga), including state estimation, and simulations to estimate a utilisation distribution. In the zebra analysis, we identified two behavioural states, with clearly distinct patterns of movement and habitat selection ("encamped" and "exploratory"). In particular, although the zebra tended to prefer areas higher in grassland across both behavioural states, this selection was much stronger in the fast, directed exploratory state. We also found a clear diel cycle in behaviour, which indicated that zebras were more likely to be exploring in the morning and encamped in the evening. This method can be used to analyse behaviour-specific habitat selection in a wide range of species and systems. A large suite of statistical extensions and tools developed for HMMs and SSFs can be applied directly to this integrated model, making it a very versatile framework to jointly learn about animal behaviour, habitat selection, and space use.

ecology↗

Multiple mechanisms prevent ectopic condensation of FG nucleoporins in the cytoplasm

Nucleoporins (Nups) assemble nuclear pores that form the permeability barrier that separates nucleoplasm from cytoplasm. Nups have also been observed in cytoplasmic foci proposed to function as pore pre-assembly intermediates. Here we characterize the composition and incidence of cytoplasmic Nup foci in an intact animal, C. elegans. We find that, in young non-stressed animals, Nup foci only appear in developing sperm, oocytes, and embryos, tissues that express high Nup levels. The foci are condensates of highly cohesive FG-Nups that are maintained near their solubility limit in the cytoplasm by posttranslational modifications and chaperone activity. Only a minor fraction of FG-Nup molecules concentrate in Nup foci, which dissolve during M phase and are dispensable for nuclear pore assembly. Nup condensation is enhanced by stress and advancing age, and overexpression of a single FG-Nup in post-mitotic neurons is sufficient to induce ectopic condensation and organismal paralysis. Our results suggest that Nup foci are non-essential, "accidental", and potentially toxic condensates whose assembly is actively suppressed in healthy cells.

cell biology↗